Circulating adhesion molecules in obstructive sleep apnea and cardiovascular disease

Abstract

Over 20 years of evidence indicates a strong association between obstructive sleep apnea (OSA) and cardiovascular disease. Although inflammatory processes have been heavily implicated as an important link between the two, the mechanism for this has not been conclusively established. Atherosclerosis may be one of the mechanisms linking OSA to cardiovascular morbidity. This review addresses the role of circulating adhesion molecules in patients with OSA, and how these may be part of the link between cardiovascular disease and OSA. There is evidence for the role of adhesion molecules in cardiovascular disease risk. Some studies, albeit with small sample sizes, also show higher levels of adhesion molecules in patients with OSA compared to controls. There are also studies that show that levels of adhesion molecules diminish with continuous positive airway pressure therapy. Limitations of these studies include small sample sizes, cross-sectional sampling, and inconsistent control for confounding variables known to influence adhesion molecule levels. There are potential novel therapies to reduce circulating adhesion molecules in patients with OSA to diminish cardiovascular disease. Understanding the role of cell adhesion molecules generated in OSA will help elucidate one mechanistic link to cardiovascular disease in patients with OSA.

Keywords: Adhesion molecules; Atherosclerosis; Cardiovascular diseases; Epidemiological studies; Sleep apnea.

Fig. 1

Schematic illustration of obstructive sleep apnea and the link to atherosclerosis and cardiovascular disease, including the role of adhesion molecules. CRP, C-reactive protein; ICAM-1; intercellular adhesion model-1; IL-6, interleukin-6; IL-8, interleuken-8; MCP-1, monocyte chemoattractant protein-1; NF-κB, nuclear factor-kappa B; TNF-α, tumor necrosis factor-α; VCAM-1, vascular cell adhesion model-1.

Fig. 2

Leukocyte recruitment process. Leukocytes in the bloodstream tether and roll onto an inflamed endothelium via interactions between selectins and their respective ligands. The defined general sequence of events includes tethering, rolling, adhesion, and transmigration. Chemokines and or other proinflammatory mediators are released by various sources within the tissue (e.g., mast cells) and are presented on the endothelium to the rolling leukocytes. This action results in integrin activation and firm adhesion followed by transmigration into the site of inflammation. Reproduced with permission from Kubes and Kerfoot with a modified legend.